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Adult Diffuse Large B-Cell LymphomaPhase 2NCT00992446

Bortezomib and Vorinostat as Maintenance Therapy After Autologous Stem Cell Transplant in Treating Patients With Non-Hodgkin Lymphoma

A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Bortezomib and Carmustine in people with Adult Diffuse Large B-Cell Lymphoma and B-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This phase II trial studies the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma (NHL) after patients' own stem cell (autologous) transplant. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Autologous Hematopoietic Stem Cell Transplantation, Bortezomib and Carmustine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
27 participants
Where
1 siteUnited States
Study dates
2 Sep 2010to 29 Oct 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosis of non-Hodgkin's lymphoma, transformed B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell or T-cell lymphoma, and deemed a candidate for autologous transplant
  • American Heart Association class I: patients with cardiac disease but without resulting limitation of physical activity; ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain; additionally, patients > 60 years of age must have a left ventricular ejection fraction of at least >= 40% demonstrated by multi gated acquisition scan (MUGA) or echocardiogram (Echo)
  • Total bilirubin =< 1.5 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x the upper limit of normal
  • Creatinine clearance (CrCL) (calculated creatinine clearance is permitted) > 40 mL/min
  • Diffusing capacity of the lung for carbon monoxide (DLCO), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) >= 50% of predicted (corrected for hemoglobin)
Show all 17Show fewer
  • Autologous graft with a minimum of >= 3.0 x 10^6 CD34+ cells/kg; not CD34 selected
  • Signed informed consent
  • Female patients of childbearing potential has a negative serum pregnancy test beta-human chorionic gonadotropin (hCG)
  • Female patient is either postmenopausal, free from menses for >= 2 years, surgically sterilized, or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study
  • Male patient agrees to use an adequate method of contraception for the duration of the study
  • 30-120 days post ASCT for non-Hodgkin's lymphoma
  • CrCL >= 40 ml/min
  • Platelets (PLT) >= 75,000 cells/mm^3 for 5 days after recovery from ASCT nadir
  • Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 for 5 days after recovery from ASCT nadir
  • Total bilirubin (TB) =< 1.5 x upper limit of normal (ULN)
  • AST/ALT =< 2.5 x ULN

Who cannot join

  • Karnofsky performance score < 70%
  • Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement)
  • Pregnant or breastfeeding
  • Fertile men and women unwilling to use contraceptive techniques from the time of transplant until one month post maintenance therapy
  • Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)
  • Patients with evidence of myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML) or abnormal cytogenetics analysis indicative of MDS on the pre-transplant bone marrow examination
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  • Prolonged corrected QT interval (QTC) on electrocardiogram (EKG)
  • Poorly-controlled diabetes mellitus (DM)
  • >= grade 2 peripheral neuropathy
  • Prior history of human immunodeficiency virus (HIV) positivity or known history of hepatitis B or C
  • Previous history of hypersensitivity to bortezomib, boron, or mannitol; known hypersensitivity to the components of study drug or its analogs
  • Require therapeutic anticoagulation treatment, especially with Coumadin
  • Patient who has had chemotherapy, radiotherapy, or biological therapy, within 30 days (42 days for nitrosoureas or mitomycin C) or who has not recovered from adverse events due to agents administered more than 30 days earlier
  • Patient is currently participating or has participated in a study with an investigational compound or devise within 30 days of initial dosing with study drug(s)
  • Patient had prior treatment with an histone deacetylase (HDAC) inhibitor (e.g., romidepsin [Depsipeptide], NSC-630176, MS 275, LAQ-824, belinostat [PXD-101], LBH589, MGCD0103, CRA024781, etc); patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study; patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period
  • History of central nervous system (CNS) disease
  • Symptomatic ascites or pleural effusions
  • Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse
  • Patient with a history of a prior malignancy with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma or an in situ malignancy; adequately treated localized prostate carcinoma with prostate-specific antigen (PSA) < 1.0; or who has undergone potentially curative therapy with no evidence of disease for five years, and/or who is deemed at low risk for recurrence by his/her treating physician
  • Patient has a history or current evidence of any condition, therapy, or laboratory (lab) abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate
  • Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs
  • >= grade 2 peripheral neuropathy within 14 days before beginning maintenance therapy
  • Prolonged QTC
  • Poorly-controlled DM
  • Myocardial infarction (MI) with ASCT or developed dilated cardiomyopathy with ASCT
  • Untreated systemic infection
  • Potassium (K) and magnesium (Mg) >= grade 2 toxicity
  • Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities; prior to study entry, any electrocardiogram (ECG) abnormality at screening must be documented by the investigator as not medically relevant
  • Patient has hypersensitivity to VELCADE (bortezomib), boron, or mannitol
  • Female subject is pregnant or lactating; confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening; pregnancy testing is not required for postmenopausal or surgically sterilized women
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on day 1 before first dose of study drug, if applicable
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy
  • Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial
  • Radiation therapy within 3 weeks before randomization; enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Bortezomib* and Vorinostat as Maintenance Therapy After Autologous Transplant for Non-Hodgkin Lymphoma Using R-BEAM or BEAM Conditioning Transplant Regimen

This phase II trial studies the side effects and how well bortezomib and vorinostat work in treating patients with non-Hodgkin lymphoma (NHL) after patients' own stem cell (autologous) transplant. Bortezomib and vorinostat in the laboratory may stop the growth of lymphoma cells and make them more likely to die by blocking some of the enzymes needed for cell growth. Giving bortezomib together with vorinostat after an autologous stem cell transplant may thus kill lymphoma cells that remain after transplant.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess toxicities of combining vorinostat and bortezomib as maintenance therapy after autologous stem cell transplant (ASCT) for NHL.

SECONDARY OBJECTIVES:

  1. Ability to complete planned therapy.

II. Time to disease progression, event-free survival.

III. Overall survival.

OUTLINE:

All patients receive carmustine intravenously (IV) over 3 hours on day -7; cytarabine IV twice daily (BID) over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of cluster of differentiation (CD)20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat orally (PO) once daily (QD) on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for at least 2 years.

Being tested
Autologous Hematopoietic Stem Cell Transplantation, Bortezomib, Carmustine, Cytarabine, Etoposide
Keywords
Autologous stem cell transplant, NHL, maintenance therapy
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, B-Cell, Lymphoma, Follicular, Lymphoma, Mantle-Cell, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Hematopoietic Stem Cell TransplantationProcedure or surgery

    Also called Autologous Stem Cell Transplantation

    Undergo ASCT

  • BortezomibDrug

    Also called [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341

    Given IV

  • CarmustineDrug

    Also called BCNU, Becenum, Becenun, BiCNU

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine

    Given IV

  • EtoposideDrug

    Also called Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar

    Given IV

  • MelphalanDrug

    Also called Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard

    Given IV

  • RituximabDrug

    Also called BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102

    Given IV

  • VorinostatDrug

    Also called L-001079038, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid

    Given PO

Study groups in NCT00992446
Study groupRoleWhat they receive
Treatment (chemotherapy, ASCT, bortezomib, vorinostat))ExperimentalAll patients receive carmustine IV over 3 hours on day -7; cytarabine IV BID over 3 hours and etoposide IV BID over 2 hours on days -6 to -3; and melphalan IV over 30 minutes on day -2. Only patients with history of CD20+ NHL receive additional rituximab IV on days -19 and -12. Patients undergo ASCT on day 0. Patients then receive bortezomib IV on days 2 and 8, and vorinostat PO QD on days 1-14. Treatment with bortezomib and vorinostat repeats for total of 12 courses in the absence of disease progression or unacceptable toxicity.
Receives: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Bortezomib; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Melphalan; Drug: Rituximab; Drug: Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant

    Number of patients on maintenance therapy post-transplant who experienced grade 3 or higher toxicity per NCI-Common Terminology Criteria for Adverse Events, version 3. The first three months of bortezomib and vorinostat therapy will be used as the time period to evaluate toxicity for stopping rules of the study. Toxicity that meets stopping rules will be determined based on the number of patients that are withdrawn from study for significant toxicity (grade IV, non-hematological, non-metabolic, non-peripheral neuropathy).

    Measured: 3 months after start of maintenance therapy

Secondary outcomes (4)

  1. Median Time to Disease Progression

    median days from transplant to relapse/progression

    Measured: time post ASCT to progression

  2. Ability to Complete Planned 12 Cycles of Maintenance Therapy

    Number of patients who completed all 12 cycles of maintenance therapy.

    Measured: Approximately 12 months following start of maintenance therapy

  3. Overall Survival

    Number of patients alive who received maintenance therapy

    Measured: 6.64 Years Post-Transplant

  4. Event-free Survival

    Number of patients alive without disease progression/relapse

    Measured: 6.64 Years Post-Transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Oct 2009 (estimated)
  2. Study start2 Sep 2010
  3. Primary completion17 Jun 2015
  4. Study completion29 Oct 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
27 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00992446
Sponsor's protocol ID
2292.00
Other IDs
NCI-2009-01302, FH 2292/X05287, X05287, 2292.00, P30CA015704
Status last verified
Feb 2020
First submitted
7 Oct 2009
Last updated
18 Mar 2020
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Autologous Hematopoietic Stem Cell Transplantation, Bortezomib and Carmustine in people with Adult Diffuse Large B-Cell Lymphoma and B-Cell Non-Hodgkin Lymphoma, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Toxicity of Vorinostat Bortezomib Maintenance Therapy After Autologous Transplant (time frame: 3 months after start of maintenance therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00992446.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2020.

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